Mucinous adenocarcinomas: Poor prognosis in metastatic colorectal cancer

Mekenkamp, L.; Heesterbeek, Karin J.; Koopman, Miriam; Tol, Jolien; Teerenstra, Steven; Venderbosch, Sabine; Punt, Cornelis J.A.; Nagtegaal, Irıs D.

doi:10.1016/j.ejca.2011.12.004

Cited by 142 publications

(135 citation statements)

References 35 publications

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“…Furthermore, the cancer stages were not taken into consideration. Patients with MA had worse survival than patients with AD in stage III diseases, while no such difference was observed in patients with stage IV [17,24]. Therefore, the heterogeneity of stages may explain some of the contradictions.…”

Section: Discussionmentioning

confidence: 84%

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colorectal mucinous adenocarcinoma (MA) has been associated with a worse prognosis than adenocarcinoma (AD) in advanced stages. Little is known about the prognostic impact of a mucinous histotype on the early stages of colorectal cancer with negative lymph node (LN) metastasis. In contrast to the established prognostic factors such as T stage and grading, the histological subtype is not thought to contribute to the therapeutic outcome, although different subtypes can potentially represent different entities. In this study, we aimed to define the prognostic value of mucinous histology in colorectal cancer with negative LNs. Methods: Between 2006 and 2017, a total of 4893 consecutive patients without LN metastasis underwent radical surgery for primary colorectal cancer (MA and AD) in Fudan University Shanghai Cancer Center (FUSCC). Clinical, histopathological, and survival data were analyzed. Results: The incidence of MA was 11% in 4893 colorectal cancer patients without LN metastasis. The MA patients had a higher T category, a greater percentage of LN harvested, larger tumor size and worse grading than the AD patients (p < 0.001 for each). We found that MA histology was correlated with a poor prognosis in terms of relapse in node-negative patients, and MA histology combined with TNM staging may be a feasible method for predicting the relapse rate. Additionally, MA presented as a high-risk factor in patients with negative perineural or vascular invasion and well/moderate-differentiation and showed a more dismal prognosis for stage II patients. Meanwhile, the disease-free survival was identical in MA and AD patients after neo- and adjuvant chemotherapy. Conclusion: MA histology is an independent predictor of poor prognosis due to relapse in LN-negative colorectal cancer patients. Mucinous histology can suggest a possible high risk in early-stage colorectal carcinoma.

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Section: Discussionmentioning

confidence: 84%

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

et al. 2018

Cell Physiol Biochem

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“…Several studies reported that patients with colorectal mucinous adenocarcinoma had a poorer prognosis compared with that of patients with non-mucinous adenocarcinoma (57)(58)(59). Differences in metastatic patterns between histological subtypes of colorectal cancer and a high number of peritoneal metastases in colorectal mucinous adenocarcinomas have also been reported (60)(61)(62)(63). However, the underlying mechanisms for the differences in metastatic patterns between various histological subtypes remain unclear.…”

Section: Discussionmentioning

confidence: 98%

Nuclear expression of claudin‑3 in human colorectal adenocarcinoma cell lines and tissues

et al. 2017

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Abstract.Claudins are members of a large family of transmembrane proteins, which are essential for the formation of tight junctions and have a significant effect on the biological behavior of tumor progression. Previous studies have demonstrated that several claudins show aberrant expression patterns in numerous types of cancer. The present study investigated the expression and localization of claudin-3 and claudin-7 in human colorectal adenocarcinoma cell lines and tissues. The protein expression levels of claudin-3 and claudin-7 were determined using immunocytochemical and immunohistochemical staining. Claudin-3, but not claudin-7, exhibited nuclear localization in the human colorectal adenocarcinoma Caco-2 and SW620 cell lines. Surgically resected colorectal adenocarcinoma tissue specimens were obtained, and the associations between the expression of claudin-3 or claudin-7 and various clinicopathological parameters were analyzed. The membranous expression rates of claudin-3 and claudin-7 were 58.0 and 50.0%, while their nuclear expression rates were 22.0 and 2.0%, respectively. The membranous expression of claudin-3 and claudin-7 was not associated with any clinicopathological factors, whereas the nuclear expression of claudin-3 was associated with histological type and was significantly increased in colorectal mucinous adenocarcinomas compared with that in well-to moderately-differentiated colorectal adenocarcinomas (P<0.01). However, no associations were observed between the nuclear expression of claudin-7 and any clinicopathological parameter. In conclusion, the nuclear expression of claudin-3 in colorectal mucinous adenocarcinoma may be involved in the biological transformation of tumors. The results from the present study indicated that claudin-3 is an important protein associated with histological type and has potential as a prognostic marker. Although the mechanisms underlying the nuclear localization of claudin-3 in tumorigenesis have not yet been elucidated in detail, the present results indicated the potential of claudin-3 as a histopathological biomarker for colorectal adenocarcinomas.

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“…Many of these studies investigated adjuvant chemotherapeutic strategies and only few observed outcome and OS of patients who received palliative treatment for metastatic CRC [21-24]. Theoretically, one would expect a worse response to chemotherapy in mucinous cancers, as they contain a higher rate of microsatellite instable tumors and B-Raf proto-oncogene, serine/threonine kinase mutations (but also phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha and transforming growth factor beta mutations [21]) compared to nonmucinous tumors [22], which previously have been demonstrated to be linked to a worse prognosis. However, most of the studies investigating efficacy of chemotherapeutic treatment in mucinous CRC were rather small [23-25] and by far not sufficient for obtaining reliable data.…”

Section: Discussionmentioning

confidence: 99%

Advanced Mucinous Colorectal Cancer: Epidemiology, Prognosis and Efficacy of Chemotherapeutic Treatment

Ott¹,

Gerken

Hirsch

et al. 2018

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Background: The clinicopathological significance of the mucinous subtype of colorectal cancer (CRC) remains controversial. As of today, none of the current guidelines differentiate treatment with respect to mucinous or nonmucinous cancer. Due to the lack of substantiated data, best treatment remains unclear and the mucinous subtype of CRC is usually treated along the lines of recommendations for adenocarcinoma of the colon. Methods: We investigated an East-Bavarian cohort of 8,758 patients with CRC. These included 613 (7.0%) patients with a mucinous subtype, who were analyzed for assessing their characteristics in clinical course and for evaluating the efficacy of common chemotherapy protocols. Results and Conclusion: Mucinous CRC was predominantly located in the right hemicolon; it was diagnosed at more advanced stages and occurred with preponderance in women. A higher rate of G3/4 grading was observed at diagnosis (all p < 0.001). An association of mucinous CRC with younger age at initial diagnosis, previously reported by other groups, could not be confirmed. Patients with mucinous stage IV colon cancer demonstrated poorer survival (p = 0.006). In contrast, no differences in survival were observed for specific stages I–III colon cancer. Stage-dependent analysis of rectal cancer stages I–IV also showed no differences in survival. However, univariable overall analysis resulted in significant poorer survival of mucinous compared to nonmucinous rectal cancer (p = 0.029). Also, combined analysis of all patients with mucinous CRC revealed poorer overall survival (OS) of these patients compared to nonmucinous CRC patients (median 48.4 vs. 60.2 months, p = 0.049) but not in multivariable analysis (p = 0.089). Chemotherapeutic treatment showed comparable efficacy regarding OS for mucinous and nonmucinous cancers in both an adjuvant and palliative setting for colon cancer patients (p values comparing mucinous and nonmucinous cancers < 0.001–0.005).

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Mucinous adenocarcinomas: Poor prognosis in metastatic colorectal cancer

Cited by 142 publications

References 35 publications

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

Mucinous Adenocarcinomas Histotype Can Also be a High-Risk Factor for Stage II Colorectal Cancer Patients

Nuclear expression of claudin‑3 in human colorectal adenocarcinoma cell lines and tissues

Advanced Mucinous Colorectal Cancer: Epidemiology, Prognosis and Efficacy of Chemotherapeutic Treatment

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